Method for treating psoriasis

ABSTRACT

A method for treating psoriasis including the steps of applying an isothiocyanate functional surfactant to an area affected by psoriasis, wherein the isothiocyanate functional surfactant comprises at least one isothiocyanate functional group associated with an aliphatic and/or aromatic carbon atom of the isothiocyanate functional surfactant.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/351,616, entitled “METHOD FOR TREATING PSORIASIS,” filed Jan. 17,2012, now U.S. Pat. No. 9,532,969 which claims the benefit of U.S.Provisional Application Ser. No. 61/440,608, entitled “METHOD FORTREATING PSORIASIS,” filed Feb. 8, 2011 and U.S. Provisional ApplicationSer. No. 61/502,090, entitled “METHOD FOR TREATING PSORIASIS,” filedJun. 28, 2011—all of which are hereby incorporated herein by referencein their entirety, including all references cited therein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates in general to a method for treatingpsoriasis and, more particularly, to a method for treating a pluralityof forms of psoriasis including, but not limited to, plaque psoriasis,guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermicpsoriasis, scalp psoriasis, and nail psoriasis—just to name a few.

2. Background Art

According to the National Institutes of Health, psoriasis is a chronic,autoimmune disease, which affects approximately 7 to 10 millionAmericans, and approximately 80 to 120 million individuals worldwide.

Psoriasis typically manifests physical symptoms on the skin of anindividual, and is believed to occur when the individual's immune systemsends out faulty and/or inaccurate signals that speed up the growthcycle of skin cells. Psoriasis is not believed to be contagious.

Psoriasis is generally, but not always, characterized by patches ofthick, red, inflamed skin and dry, silvery flakes of skin known asscales. Symptoms range in severity from barely noticeable to severeoutbreaks of lesions that cover most of the body.

Forms of Psoriasis.

There are seven general forms of psoriasis, namely: plaque, guttate,inverse, pustular, erythrodermic, scalp, and nail.

(I) Plaque psoriasis (i.e., psoriasis vulgaris) is the most prevalentform of the disease. About 80 percent of those who have psoriasis havethis type. Plaque psoriasis is normally characterized by raised,inflamed, red lesions covered by a silvery white scale. It is typicallyfound on the elbows, knees, scalp and/or the lower back of anindividual.

(II) Guttate psoriasis is a form of psoriasis that often starts inchildhood or young adulthood. The word guttate is derived from the Latinword meaning “drop.” This form of psoriasis appears as small, red,individual spots on the skin. Guttate lesions usually appear on thetrunk and limbs. These spots are not usually as thick as plaque lesions.Guttate psoriasis, often times, comes on quite suddenly. A variety ofconditions can bring on an attack of guttate psoriasis, including upperrespiratory infections, streptococcal throat infections (i.e., strepthroat), tonsillitis, stress, injury to the skin and/or theadministration of certain drugs including, but not limited to,antimalarials and beta-blockers.

(III) Inverse psoriasis is typically found in the armpits, groin, underthe breasts, and in other skin folds around the genitals and thebuttocks. This type of psoriasis appears as bright-red lesions that aresmooth and shiny. Inverse psoriasis is subject to irritation fromrubbing and sweating because of its location in skin folds and tenderareas. Inverse psoriasis can be more troublesome in overweight peopleand those with deep skin folds.

(IV) Pustular psoriasis, which is often seen in adults, is characterizedby white blisters of noninfectious pus (comprising of white blood cells)surrounded by red skin. Pustular psoriasis may be localized to certainareas of the body, such as the hands and feet, or covering most of thebody. It typically begins with the reddening of the skin followed byformation of pustules and scaling.

Pustular psoriasis may be triggered by internal medications, irritatingtopical agents, overexposure to electromagnetic radiation (e.g.,ultraviolet (UV) radiation), pregnancy, systemic steroids, infections,stress and/or sudden withdrawal of systemic medications and/or potenttopical steroids.

(V) Erythrodermic psoriasis is a particularly inflammatory form ofpsoriasis that affects most of the body surface. It may occur inassociation with pustular psoriasis, and is characterized by periodic,widespread, fiery redness of the skin and the shedding of scales insheets, rather than smaller flakes. The reddening and shedding of theskin are often accompanied by severe itching and pain, heart rateincrease, and fluctuating body temperature. Erythrodermic psoriasis canbe very serious and can causes protein and/or fluid loss that can leadto severe and prolonged illness. Erythrodermic psoriasis may also bringon infection, pneumonia, and congestive heart failure. People withsevere cases of this condition often require hospitalization.

Known triggers of erythrodermic psoriasis include the abrupt withdrawalof a systemic psoriasis treatment including cortisone, allergic reactionto a drug resulting in the Koebner response, severe sunburns, infection,and medications such as lithium, anti-malarial drugs; and strong coaltar products.

(VI) Scalp psoriasis appears as red, itchy areas with silvery whitescales on the scalp. One may notice flakes of dead skin in hair or onthe shoulders, especially after scratching the scalp.

(VII) Nail psoriasis can affect both fingernails and toenails, causingpitting, abnormal nail growth and discoloration. Psoriatic nails maybecome loose and separate from the nail bed (i.e., onycholysis). Severecases of nail psoriasis may cause the nail to crumble.

While no one knows exactly what causes psoriasis, it is believed thatthe immune system and/or genetics play substantial roles in itsdevelopment. Most researchers agree that the immune system is somehowmistakenly triggered and/or excited, which causes a series of events,including acceleration of skin cell growth. A normal skin cell maturesand falls off the body in approximately 28 to 30 days. A skin cell in apatient with psoriasis takes only 3 to 4 days to mature and instead offalling off (shedding), the cells pile up on the surface of the skin,forming psoriatic lesions.

Scientists believe that at least 10 percent of the general populationinherits one or more of the genes that create a predisposition topsoriasis. However, only about 2-5 percent of the population developsthe disease. Researchers believe that for a person to develop psoriasis,the individual likely has a combination of the genes that causepsoriasis and is exposed to specific external factors known as“triggers.”

Psoriasis triggers are not believed to be universal. As such, what maycause one individual's psoriasis to become active, may not affectanother. However, generally established psoriasis triggers include:stress, injury to the skin (e.g., Koebner phenomenon), and medications(e.g., lithium, antimalarials, plaquenil, quinacrine, chloroquine,hydroxychloroquine, beta-blockers, inderal, quinidine, indomethacin,etcetera).

Although scientifically unproven, some people with psoriasis suspectthat alcohol consumption, allergies, diet, infections, smoking, stress,and weather trigger their psoriasis.

To the best of Applicant's knowledge, there is no known cure forpsoriasis. Treatments for psoriasis are typically divided into threemain types, namely: topical treatments, light therapy and/or oralmedications.

Topical treatments include, for example, corticosteroids, vitamin Danalogues, anthralin, retinoids, calcineurin inhibitors, salicylic acid,coal tar, and moisturizers.

Light therapy or treatments include, for example, sunlight, UVBphototherapy, narrowband UVB therapy, photochemotherapy, or psoralenplus ultraviolet A (PUVA), and excimer laser.

Oral medications include, for example, retinoids, methotrexate,cyclosporine, hydroxyurea, immunomodulator drugs (biologics).

While the above-identified medical treatments do appear to provide atleast some relief to those who are afflicted by psoriasis, suchtreatment remains non-desirous and/or problematic inasmuch as, amongother things, none of the above-identified treatments provide sufficienttherapeutic relief from the debilitating effects of psoriasis withoutmaterial drawbacks.

It is therefore an object of the present invention to provide a methodfor treating psoriasis which offers timely relief from the symptomspresented when one is afflicted with psoriasis.

These and other objects of the present invention will become apparent inlight of the present specification, claims, and drawings.

SUMMARY OF THE INVENTION

In one embodiment, the present invention is directed to a method fortreating psoriasis comprising the step of: applying an isothiocyanatefunctional surfactant to an area affected by psoriasis, wherein theisothiocyanate functional surfactant comprises at least oneisothiocyanate functional group associated with an aliphatic and/oraromatic carbon atom of the isothiocyanate functional surfactant.

In another embodiment of the present invention, the method for treatingpsoriasis further comprises the step of removing the isothiocyanatefunctional surfactant from the area affected by psoriasis.

In yet another exemplary embodiment, the present invention is directedto a method for treating psoriasis comprising the steps of: (a) applyingan isothiocyanate functional surfactant to an area affected bypsoriasis, wherein the isothiocyanate functional surfactant comprises atleast one isothiocyanate functional group associated with an aliphaticand/or aromatic carbon atom of the isothiocyanate functional surfactant;(b) removing the isothiocyanate functional surfactant from the areaaffected by psoriasis; and (c) repeating the steps of applying andremoving the isothiocyanate functional surfactant to/from the affectedarea.

The present invention is also directed to a method for treatingpsoriasis comprising the step of: washing an area affected by psoriasiswith an isothiocyanate functional surfactant, wherein the isothiocyanatefunctional surfactant comprises at least one isothiocyanate functionalgroup associated with an aliphatic and/or aromatic carbon atom of theisothiocyanate functional surfactant.

The present invention is further directed to a method for treatingpsoriasis comprising the step of: applying a lysine derivative to anarea affected by psoriasis, wherein the lysine derivative comprises anα-nitrogen and a ε-nitrogen, and wherein an alkyl and/or alkanoylsubstituent comprising at least approximately 8 carbon atoms isassociated with the α-nitrogen, and further wherein at least oneisothiocyanate functional group is associated with the ε-nitrogen.

The present invention is still further directed to a method for treatingpsoriasis comprising the step of: applying a surfactant to an areaaffected by psoriasis, wherein the protonated form of the surfactant isrepresented by the following chemical structure:

wherein the surfactant comprises a non-polar moiety (NP) and a polarmoiety (P), and wherein at least one isothiocyanate functional group(NCS) is associated with the polar and/or non-polar moiety.

In another embodiment, the present invention is directed to a method fortreating psoriasis, comprising the step of: applying a surfactant or apharmaceutically acceptable salt thereof to an area affected bypsoriasis, wherein the protonated form of the surfactant is representedby the following chemical structure:

wherein R₁ comprises an alkyl, cycloalkyl, polycycloalkyl,heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl,alkenyl, alkynyl and/or cyano group containing approximately 1 toapproximately 25 carbon atom(s), wherein the carbon atom(s) may be alinking group to, or part of, a halogen, a N, O, and/or S containingmoiety, and/or one or more functional groups comprising alcohols,esters, ammonium salts, phosphonium salts, and combinations thereof; alinkage to a dimer; a linkage to an oligomer; and/or a linkage to apolymer; wherein R₂ comprises NCS; and wherein R₃-R₅ are the same ordifferent and comprise H; OH; an alkyl, cycloalkyl, polycycloalkyl,heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl,alkenyl, alkynyl and/or cyano group containing approximately 1 toapproximately 25 carbon atom(s), wherein the carbon atom(s) may be alinking group to, or part of, a halogen, a N, O, and/or S containingmoiety, and/or one or more functional groups comprising alcohols,esters, ammonium salts, phosphonium salts, and combinations thereof; alinkage to a dimer; a linkage to an oligomer; and/or a linkage to apolymer with the proviso that at least one of R₃-R₅ comprise an alkyl,cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl,alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containingapproximately 8 to approximately 25 carbon atom(s).

The present invention is also directed to a method for treatingpsoriasis comprising the step of: applying a surfactant or apharmaceutically acceptable salt thereof to an area affected bypsoriasis, wherein the protonated form of the surfactant is representedby the following chemical structure:

wherein X comprises an integer ranging from approximately 1 toapproximately 25, and wherein Y comprises an integer ranging fromapproximately 6 to approximately 25.

In a preferred embodiment, the present invention is directed to a methodfor treating psoriasis comprising the step of: applying a surfactant ora pharmaceutically acceptable salt thereof to an area affected bypsoriasis, wherein the protonated form of the surfactant is representedby the following chemical structure:

In another embodiment, the present invention is directed to a method fortreating psoriasis, comprising the step of: applying a surfactant or apharmaceutically acceptable salt thereof to an area affected bypsoriasis, wherein the deprotonated form of the surfactant isrepresented by the following chemical structure:

wherein R₁ comprises an alkyl, cycloalkyl, polycycloalkyl,heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl,alkenyl, alkynyl and/or cyano group containing approximately 1 toapproximately 25 carbon atom(s), wherein the carbon atom(s) may be alinking group to, or part of, a halogen, a N, O, and/or S containingmoiety, and/or one or more functional groups comprising alcohols,esters, ammonium salts, phosphonium salts, and combinations thereof; alinkage to a dimer; a linkage to an oligomer; and/or a linkage to apolymer; wherein R₂ comprises NCS; wherein R₃-R₅ are the same ordifferent and comprise H; OH; an alkyl, cycloalkyl, polycycloalkyl,heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl,alkenyl, alkynyl and/or cyano group containing approximately 1 toapproximately 25 carbon atom(s), wherein the carbon atom(s) may be alinking group to, or part of, a halogen, a N, O, and/or S containingmoiety, and/or one or more functional groups comprising alcohols,esters, ammonium salts, phosphonium salts, and combinations thereof; alinkage to a dimer; a linkage to an oligomer; and/or a linkage to apolymer with the proviso that at least one of R₃-R₅ comprise an alkyl,cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl,alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containingapproximately 8 to approximately 25 carbon atom(s), wherein X comprisesa counter cation such as, but not limited to, alkali metals, alkalineearth metals, transition metals, s-block metals, d-block metals, p-blockmetals, NZ₄ ⁺, wherein Z comprises, H, R₆, and/or OR₆, and wherein R₆comprises an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl,alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyanogroup containing approximately 1 to approximately 25 carbon atom(s),wherein the carbon atom(s) may be a linking group to, or part of, ahalogen, a N, O, and/or S containing moiety, and/or one or morefunctional groups comprising alcohols, esters, ammonium salts,phosphonium salts, and combinations thereof; a linkage to a dimer; alinkage to an oligomer; and/or a linkage to a polymer.

In yet another preferred embodiment, the present invention is directedto a method for treating psoriasis as disclosed supra, furthercomprising the step of applying an additional surfactant, wherein theadditional surfactant is selected from at least one of the groupcomprising a non-ionic surfactant, an anionic surfactant, a cationicsurfactant, a zwitterionic surfactant, and combinations thereof.

DETAILED DESCRIPTION OF THE INVENTION

While this invention is susceptible of embodiment in many differentforms, there is shown in the drawings and described herein in detailseveral specific embodiments with the understanding that the presentdisclosure is to be considered as an exemplification of the principlesof the invention and is not intended to limit the invention to theembodiments illustrated.

In accordance with the present invention, surprisingly effective methodsfor treating psoriasis are provided herein. In particular, methods fortreating a plurality of types of psoriasis including plaque psoriasis,guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermicpsoriasis, scalp psoriasis, and nail psoriasis are disclosed.

In one embodiment, the present invention is directed to a method fortreating psoriasis comprising the steps of applying one or moreisothiocyanate functional surfactants to an area affected by psoriasis.Preferably, the isothiocyanate functional surfactant comprises one ormore isothiocyanate functional groups associated with an aliphaticand/or aromatic carbon atom of the isothiocyanate functional surfactant.It will be understood that an area affected by psoriasis may compriseareas proximate and/or contiguous to areas where a manifestation ofphysical symptoms are present. Physical symptoms include, for example,discomfort, itching, burning, erythema, blistering, scaling, epidermalnecrosis, desquamation, discoloration, and/or hyperpigmentation—just toname a few. It will be further understood that isothiocyanate functionalsurfactants, regardless of their ordinary meaning, are defined herein asa surfactant having an isothiocyanate functional group associatedtherewith. It will be yet further understood that the term associated asused herein in chemical context, regardless of its ordinary meaning, isdefined herein as attached, a covalent bond, a polar covalent bond, anionic bond, a hydrogen bond, van der Waals forces, electrostaticinteraction, directly and/or indirectly linked, etcetera.

The term surfactant derives from contraction of the termssurface-active-agent and is defined herein as a molecule and/or group ofmolecules which are able to modify the interfacial properties of theliquids (aqueous and non-aqueous) in which they are present. Thesurfactant properties of these molecules reside in their amphiphiliccharacter which stems from the fact that each surfactant molecule hasboth a hydrophilic moiety and a hydrophobic (or lipophilic) moiety, andthat the extent of each of these moieties is balanced so that atconcentrations at or below the critical micelle concentration (i.e.,CMC) they generally concentrate at the air-liquid interface andmaterially decrease the interfacial tension. For example, sodium saltsof saturated carboxylic acids are extremely soluble in water up to C8length and are thus not true surfactants. They become less soluble inwater from C9 up to C18 length, the domain of effective surfactants forthis class of compounds. The carboxylic acids (fatty acids) can beeither saturated or unsaturated starting from C16 chain lengths.

Without being bound by any one particular theory, it is believed thatthe isothiocyanate functional surfactants disclosed herein facilitatetreatment of numerous forms of psoriasis by boosting the body's immunesystem. It is also believed that the isothiocyanate functionalsurfactants disclosed herein facilitate elevating phase II enzymes(e.g., HAD(P)H quinine oxidoreductase) which are believed to, amongother things regulate inflammatory responses within the body, as well asdetoxify carcinogens and/or activated carcinogens.

In accordance with the present invention, the isothiocyanate functionalsurfactants may be used as a topical leave-on product in which one ormore surfactants remain on the skin and are not immediately and/or everrinsed off away from the skin. Alternatively, the isothiocyanatefunctional surfactants of the present invention may be used as a topicalwash in an apply-and-rinse fashion. For either case, it is preferredthat the isothiocyanate functional surfactants be generally mild tohuman skin (e.g., non-irritating or low-irritating). In particular,anionic N-alkanoyl surfactants derived from amino acids are especiallypreferred because, while not completely predictable, they have atendency to be mild. The methods of preparation detailed in thisinvention employ, but are not limited to, amino acids that possess atleast two amine functionalities, at least one of which is converted toan N-alkanoyl functionality, and at least one of which is converted intoisothiocyanate functionality. The amino acids include, but are notlimited to, the α-amino acids lysine, ornithine, 2,4-diaminobutanoicacid, 2,3-diaminoproprionic acid, 2,7-diaminoheptanoic acid, and2,8-diaminooctanoic acid. Additionally, amino acids other than α-aminoacids may be employed, such as β-amino acids, etcetera. It will beunderstood that amino acid derived surfactants are preferred due totheir mild nature, but any one of a number of other surfactants arelikewise contemplated for use in accordance with the present invention.

Methods for preparing isothiocyanate functional surfactants and/or theirprecursors can involve, but are not limited to, conversion of an aminefunctionality to an isothiocyanate functionality. The methods ofconversion of amine functionalities to isothiocyanate functionalitiesinclude, but are not limited to: (1) reaction with carbon disulfide toyield an intermediate dithiocarbamate, followed by reaction withethylchloroformate or its functional equivalent such asbis(trichloromethyl)-carbonate, trichloromethyl chloroformate, orphosgene; (2) reaction with thiophosgene; (3) reaction with1,1′-thiocarbonyldiimidizole; (4) reaction with phenylthiochloroformate;(5) reaction with ammonium or alkali metal thiocyanate to prepare anintermediate thiourea followed by cleaving to the isothiocyanate viaheating; and (6) reaction with an isothiocyanato acyl halide[SCN—(CH₂)_(n)—CO—Cl]. The resulting isothiocyanate functionalsurfactant, depending on the method of preparation, can be isolated as apure material or as a mixture with other surfactants. The resultingisothiocyanate functional surfactant, depending on the method ofpreparation, can be isolated and used directly in nonionic form, anionicform, cationic form, zwitterionic (amphoteric) form, and/or in a neutralsurfactant-precursor form in combination with a base such as sodiumhydroxide or triethanol amine if the neutral surfactant-precursor formpossesses a protonated carboxylic acid group such that reaction(deprotonation) with the base converts the neutral surfactant-precursorform to an anionic surfactant, or in neutral surfactant-precursor formin combination with an acid if the neutral surfactant-precursor formpossess amine functionality such that reaction (protonation) with theacid converts the neutral surfactant-precursor form to a cationicsurfactant.

In accordance with the present invention the step of applying comprises,but is not limited to, spraying, dripping, dabbing, rubbing, blotting,dipping, and any combination thereof.

In a preferred embodiment of the present invention, the isothiocyanatefunctional surfactant is removed from the affected area after a periodof time. Such a period comprises, but is not limited to, seconds (e.g.,1 second, 2 seconds, 5 seconds, 10 seconds, 15 seconds, 20 seconds, 30seconds, 45 seconds, and 60 seconds), minutes (e.g., 1 minute, 2minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45minutes, and 60 minutes), hours (e.g., 1 hour, 2 hours, 4 hours, 5hours, 8 hours, 10 hours, 15 hours, 24 hours, 36 hours, 48 hours, and 60hours), days (e.g., 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7days, 10 days, 14 days, 21 days, 30 days), etcetera. It will beunderstood that the step of removing preferably occurs via rinsing,wiping, and/or extracting—just to name a few.

Depending upon the subject and/or the severity of the psoriasis,multiple applications may be necessary. As such, the steps of applyingand/or removing the isothiocyanate functional surfactant may be repeatedone or a plurality of times.

The present invention is also directed to a method for treatingpsoriasis comprising the step of applying a lysine derivative to an areaaffected by psoriasis, wherein the lysine derivative comprises anα-nitrogen and a ε-nitrogen. Preferably, an alkyl substituent comprisingat least approximately 8 carbon atoms is associated with the α-nitrogen.Preferably, at least one isothiocyanate functional group is associatedwith the ε-nitrogen.

The present invention is further directed to a method for treatingpsoriasis comprising the step of: applying a surfactant to an areaaffected by psoriasis, wherein the surfactant is represented by thefollowing chemical structure:

and wherein the surfactant comprises a non-polar moiety (NP) and a polarmoiety (P), and wherein at least one isothiocyanate functional group(NCS) is associated with the polar and/or non-polar moiety.

The present invention is yet further directed to a method for treatingpsoriasis, comprising the step of: applying a surfactant or apharmaceutically acceptable salt thereof to an area affected bypsoriasis, wherein the protonated form of the surfactant is representedby the following chemical structure:

wherein R₁ comprises an alkyl, cycloalkyl, polycycloalkyl,heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl,alkenyl, alkynyl and/or cyano group containing approximately 1 toapproximately 25 carbon atom(s), wherein the carbon atom(s) may be alinking group to, or part of, a halogen, a N, O, and/or S containingmoiety, and/or one or more functional groups comprising alcohols,esters, ammonium salts, phosphonium salts, and combinations thereof; alinkage to a dimer; a linkage to an oligomer; and/or a linkage to apolymer; wherein R₂ comprises NCS; and wherein R₃-R₅ are the same ordifferent and comprise H; OH; an alkyl, cycloalkyl, polycycloalkyl,heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl,alkenyl, alkynyl and/or cyano group containing approximately 1 toapproximately 25 carbon atom(s), wherein the carbon atom(s) may be alinking group to, or part of, a halogen, a N, O, and/or S containingmoiety, and/or one or more functional groups comprising alcohols,esters, ammonium salts, phosphonium salts, and combinations thereof; alinkage to a dimer; a linkage to an oligomer; and/or a linkage to apolymer with the proviso that at least one of R₃-R₅ comprise an alkyl,cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl,alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containingapproximately 8 to approximately 25 carbon atom(s).

In this embodiment, the surfactant is preferably represented by thefollowing chemical structure:

wherein X comprises an integer ranging from approximately 1 toapproximately 25, and wherein Y comprises an integer ranging fromapproximately 6 to approximately 25.

More preferably, the surfactant is represented by the following chemicalstructure:

In another embodiment, the present invention is directed to a method fortreating psoriasis comprising the step of: applying a surfactant or apharmaceutically acceptable salt thereof to an area affected bypsoriasis, wherein the deprotonated form of the surfactant isrepresented by the following chemical structure:

wherein R₁ comprises an alkyl, cycloalkyl, polycycloalkyl,heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl,alkenyl, alkynyl and/or cyano group containing approximately 1 toapproximately 25 carbon atom(s), wherein the carbon atom(s) may be alinking group to, or part of, a halogen, a N, O, and/or S containingmoiety, and/or one or more functional groups comprising alcohols,esters, ammonium salts, phosphonium salts, and combinations thereof; alinkage to a dimer; a linkage to an oligomer; and/or a linkage to apolymer; wherein R₂ comprises NCS; wherein R₃-R₅ are the same ordifferent and comprise H; OH; an alkyl, cycloalkyl, polycycloalkyl,heterocycloalkyl, aryl, alkaryl, aralkyl, alkoxy, alkanoyl, aroyl,alkenyl, alkynyl and/or cyano group containing approximately 1 toapproximately 25 carbon atom(s), wherein the carbon atom(s) may be alinking group to, or part of, a halogen, a N, O, and/or S containingmoiety, and/or one or more functional groups comprising alcohols,esters, ammonium salts, phosphonium salts, and combinations thereof; alinkage to a dimer; a linkage to an oligomer; and/or a linkage to apolymer with the proviso that at least one of R₃-R₅ comprise an alkyl,cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl,alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyano group containingapproximately 8 to approximately 25 carbon atom(s), wherein X comprisesa counter cation such as, but not limited to, alkali metals, alkalineearth metals, transition metals, s-block metals, d-block metals, p-blockmetals, NZ₄ ⁺, wherein Z comprises, H, R₆, and/or OR₆, and wherein R₆comprises an alkyl, cycloalkyl, polycycloalkyl, heterocycloalkyl, aryl,alkaryl, aralkyl, alkoxy, alkanoyl, aroyl, alkenyl, alkynyl and/or cyanogroup containing approximately 1 to approximately 25 carbon atom(s),wherein the carbon atom(s) may be a linking group to, or part of, ahalogen, a N, O, and/or S containing moiety, and/or one or morefunctional groups comprising alcohols, esters, ammonium salts,phosphonium salts, and combinations thereof; a linkage to a dimer; alinkage to an oligomer; and/or a linkage to a polymer.

In accordance with the present invention, the isothiocyanate functionalsurfactant may also be associated with one or more additionalsurfactants, wherein the additional surfactants are selected from atleast one of the group comprising a non-ionic surfactant, an anionicsurfactant, a cationic surfactant, a zwitterionic surfactant, andcombinations thereof.

Non-limiting examples of preferred anionic surfactants include taurates;isethionates; alkyl and alkyl ether sulfates; succinamates; alkylsulfonates, alkylaryl sulfonates; olefin sulfonates; alkoxy alkanesulfonates; sodium and potassium salts of fatty acids derived fromnatural plant or animal sources or synthetically prepared; sodium,potassium, ammonium, and alkylated ammonium salts of alkylated andacylated amino acids and peptides; alkylated sulfoacetates; alkylatedsulfosuccinates; acylglyceride sulfonates, alkoxyether sulfonates;phosphoric acid esters; phospholipids; and combinations thereof.Specific anionic surfactants contemplated for use include, but are by nomeans limited to, ammonium cocoyl isethionate, sodium cocoylisethionate, sodium lauroyl isethionate, sodium stearoyl isethionate,sodium lauroyl sarcosinate, sodium cocoyl sarcosinate, sodium laurylsarcosinate, disodium laureth sulfosuccinate, sodium laurylsulfoacetate, sodium cocoyl glutamate, TEA-cocoyl glutamate, TEA cocoylalaninate, sodium cocoyl taurate, potassium cetyl phosphate.

Non-limiting examples of preferred cationic surfactants includealkylated quaternary ammonium salts R₄NX; alkylated amino-amides(RCONH—(CH₂)_(n))NR₃X; alkylimidazolines; alkoxylated amines; andcombinations thereof. Specific examples of anionic surfactantscontemplated for use include, but are by no means limited to, cetylammonium chloride, cetyl ammonium bromide, lauryl ammonium chloride,lauryl ammonium bromide, stearyl ammonium chloride, stearyl ammoniumbromide, cetyl dimethyl ammonium chloride, cetyl dimethyl ammoniumbromide, lauryl dimethyl ammonium chloride, lauryl dimethyl ammoniumbromide, stearyl dimethyl ammonium chloride, stearyl dimethyl ammoniumbromide, cetyl trimethyl ammonium chloride, cetyl trimethyl ammoniumbromide, lauryl trimethyl ammonium chloride, lauryl trimethyl ammoniumbromide, stearyl trimethyl ammonium chloride, stearyl trimethyl ammoniumbromide, lauryl dimethyl ammonium chloride, stearyl dimethyl cetylditallow dimethyl ammonium chloride, dicetyl ammonium chloride, dilaurylammonium chloride, dilauryl ammonium bromide, distearyl ammoniumchloride, distearyl ammonium bromide, dicetyl methyl ammonium chloride,dicetyl methyl ammonium bromide, dilauryl methyl ammonium chloride,distearyl methyl ammonium chloride, distearyl methyl ammonium bromide,ditallow dimethyl ammonium chloride, ditallow dimethyl ammonium sulfate,di(hydrogenated tallow) dimethyl ammonium chloride, di(hydrogenatedtallow) dimethyl ammonium acetate, ditallow dipropyl ammonium phosphate,ditallow dimethyl ammonium nitrate, di(coconutalkyl)dimethyl ammoniumchloride, di(coconutalkyl)dimethyl ammonium bromide, tallow ammoniumchloride, coconut ammonium chloride, stearamidopropyl PG-imoniumchloride phosphate, stearamidopropyl ethyldimonium ethosulfate,stearimidopropyldimethyl (myristyl acetate) ammonium chloride,stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyldimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate,ditallowyl oxyethyl dimethyl ammonium chloride, behenamidopropyl PGdimonium chloride, dilauryl dimethyl ammonium chloride, distearlydimethyl ammonium chloride, dimyristyl dimethyl ammonium chloride,dipalmityl dimethyl ammonium chloride, distearyl dimethyl ammoniumchloride, stearamidoproyl PG-dimonium chloride phosphate,stearamidopropyl ethyldiammonium ethosulfate, stearamidopropyl dimethyl(myristyl acetate) ammonium chloride, stearimidopropyl diemthyl cetarylammonium tosylate, stearamido propyl dimethyl ammonium chloride,stearamidopropyl dimethyl ammonium lactate.

Non-limiting examples of preferred non-ionic surfactants includealcohols, alkanolamides, amine oxides, esters (including glycerides,ethoxylated glycerides, polyglyceryl esters, sorbitan esters,carbohydrate esters, ethoxylated carboxylic acids, phosphoric acidtriesters), ethers (including ethoxylated alcohols, alkyl glucosides,ethoxylated polypropylene oxide ethers, alkylated polyethylene oxides,alkylated polypropylene oxides, alkylated PEG/PPO copolymers), siliconecopolyols. Specific examples of non-ionic surfactants contemplated foruse include, but are by no means limited to, cetearyl alcohol,ceteareth-20, nonoxynol-9, C12-15 pareth-9, POE(4) lauryl ether,cocamide DEA, glycol distearate, glyceryl stearate, PEG-100 stearate,sorbitan stearate, PEG-8 laurate, polyglyceryl-10 trilaurate, laurylglucoside, octylphenoxy-polyethoxyethanol, PEG-4 laurate, polyglyceryldiisostearate, polysorbate-60, PEG-200 isostearyl palmitate, sorbitanmonooleate, polysorbate-80.

Non-limiting examples of preferred zwitterionic or amphotericsurfactants include betaines; sultaines; hydroxysultaines, amidobetaines, amidosulfo betaines; and combinations thereof. Specificexamples of amphoteric surfactants contemplated for use include, but areby no means limited to, cocoamidopropyl sultaine, cocoamidopropylhydroxyl sultaine, cocoamidopropylbetaine, coco dimethyl carboxymethylbetaine, lauryl dimethyl carboxymethyl betaine, lauryl dimethylalphacarboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, cetyldimethyl betaine, lauryl (2-bishydroxy) carboxymethyl betaine, stearylbis-(2-hydroxyethyl) carboxymethyl betaine, oelyl dimethylgamma-carboxypropyl betaine, lauryl bis-(2-hydroxypropyl)alphacarboxymethyl betaine, coco dimethyl sulfopropyl betaine, stearyldimethyl sulfopropyl betaine, lauryl dimethyl sulfoethyl betaine, laurylbis(2-hydroxyethyl) sulfopropyl betaine, oleyl betaine, cocamidopropylbetaine.

The invention is further described by the following examples.

Example I Preparation of a mixture ofN_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysine withN_(α),N_(ε)-bis-lauroyl-L-lysine

A 1 liter beaker equipped with an overhead mechanical stainless steelpaddle stirrer was charged with 100 mL of 1 M NaOH (0.100 mol). Stirringwas initiated and the beaker cooled to −5° C. to −10° C. using asalt/ice bath. Next, 23.4 g (0.100 mol) of N_(ε)-benzylidene-L-lysine(prepared via the method of Bezas, B and Zervas, L., JACS, 83, 1961,719-722) was added. Immediately afterward and while keeping the solutioncold, 140 mL (0.140 mol) of precooled (in a salt/ice bath) 1 M NaOH and26.1 mL of lauroyl chloride was added in two equal portions over aperiod of 6 minutes. The mixture was stirred for 10 more minutes at −5to −10° C., then the ice bath was removed and the reaction mixtureallowed to stir for another 1 hour while warming to room temperature.Next, the reaction mixture was cooled using a salt/ice bath and thensufficient concentrated HCl was added to adjust the pH to 7.5-7.8. Withthe pH at 7.8-7.8 and with continued cooling and stirring, 4.6 mL (60%of stoichiometric, 0.068 mol) of thiophosgene was added drop-wise via anadditional funnel over the period of 1 hour. During this time,sufficient 1 M NaOH was added to maintain a pH range between 7.5-7.8.After the thiophosgene addition was complete, additional 1 M NaOH wasadded as necessary until the pH stabilized in 7.5-7.8 range. Next,sufficient 30% NaOH was added to adjust the pH to approximately 8.5.Next, 12 mL (0.051 mol) of lauroyl chloride was rapidly added, followedby sufficient 1 M NaOH to keep the pH in the range of 8.00-8.50. Next,sufficient concentrated HCl was added to adjust the pH to 1.5. Thereaction mixture was filtered via vacuum filtration, and the precipitatewashed with dilute HCl (pH=2). The product, a white moist solid, wasdried in vacuo while heating to 60° C. 45.19 g of white solid productwas recovered, a mixture of predominantlyN_(α)-lauroyl-N_(ε)-isothiocyanato-L-lysine andN_(α),N_(ε)-bis-lauroyl-L-lysine (determined via LC-MS analysis). Bothcompounds in this mixture can be simultaneously converted into anionic(carboxylate) surfactants via reaction with aqueous NaOH to yield aclear aqueous solution of the surfactants.

Example II Preparation of PureN_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysine Step 1: Preparation ofN_(α)-lauroyl-N_(ε)-carbobenzoxy-L-Lysine

60.0 g of N_(ε)-cbz-L-Lysine (cbz is carbobenzoxy) purchased fromAtomole Scientific Company, LTD was added to a three-liter beaker alongwith 1200 mL of RO water and the mixture was stirred. Next, 39 mL of 30%aqueous NaOH was added, resulting in dissolution of theN_(ε)-cbz-L-Lysine. The resulting solution was cooled in an ice bath andthen 52.5 mL of lauroyl chloride was added. The ice bath was removed 30minutes later, and stirring continued for an additional six hours, atwhich time 18 mL of concentrated hydrochloric acid was added. Thereaction mixture was then filtered via vacuum filtration, the whitesolid product washed with 1 M aqueous HCl, and then the solid productwas dried in vacuo while heated to approximately 85° C. 96.5 g of drywhite solid product was obtained. The product is further purified bydissolving it in methanol, filtering off any insoluble precipitate, andremoving the methanol in vacuo to recover a white solid product (mp99.5-103.0° C.).

Step 2: Preparation of N_(α)-lauroyl-N_(ε)-ammonium chloride-L-Lysine

10.0 g of N_(α)-lauroyl-N_(ε)-carbobenzoxy-L-Lysine was weighed into aone liter Erlenmeyer flask equipped with a magnetic stir bar. 150 mL ofconcentrated hydrochloric acid was added and the solution was stirredand heated in an oil bath to 104° C., then allowed to cool with the oilbath back to room temperature. The solution was then cooled to 9° C. forapproximately four hours, during which time a large mass of whiteprecipitate formed. The reaction mixture was filtered in vacuo andrinsed with a small amount of cold 1 M HCl. The white solid reactionproduct was then dried in vacuo while being heated to 78° C., yielding7.89 g of white solid product (mp 191-193° C.).

Step 3: Preparation of N_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysine

0.46 mL of thiophosgene was added to 30 mL of dichloromethane in a 125mL Erlenmeyer flask equipped with a magnetic stir bar. To this solutionwas drop wise added over 15 minutes a solution consisting of 2.00 gN_(α)-lauroyl-N_(ε)-ammonium chloride-L-Lysine, 10 mL RO water, and 2.7mL 20% aqueous NaOH. Stirring was continued for an additional 30minutes, after which sufficient concentrated hydrochloric acid was addedto lower the pH to 1 as indicated by testing with pHydrion paper. Thereaction solution was then transferred into a separatory funnel and thebottom turbid dichloromethane layer was isolated and dried withanhydrous magnesium sulfate and gravity filtered. To the filtrate wasadded 50 mL of hexanes. The solution was then concentrated via removalof 34 mL of solvent via trap-to-trap distillation and then placed in a−19° C. freezer. A mass of white precipitate formed after a few hoursand was isolated via vacuum filtration and then dried in vacuo for 2hours. 1.130 g of a slightly off white solid powder product was obtained[mp 37.0-39.0° C.; IR (cm⁻¹), 3301sb, 2923s, 2852s, 2184m, 2099s, 1721s,1650s, 1531s, 1456m, 1416w, 1347m, 1216m, 1136w]. Analysis (MidwestMicrolab, LLC): Calculated: C, 61.58%; H 9.25%; N, 7.56%; O, 12.95%; S,8.65%. Actual: C, 61.64%; H, 9.21%; N, 7.58%; O, 13.01%; S, 8.55%.

Step 4: Isolation of SodiumN_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysinate Via Lyophilization

0.147 g of N_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysine was combined andstirred with 2 g of RO water and 0.39 mL of 1.00 M NaOH in a 50 mLsingle neck round bottom flask and filtered into a 250 mL single neckround bottom flask to yield a clear pale amber solution. The flask wasthen immersed while rotating into a dry ice/acetone bath to yield asolid coating on the walls of the flask, whereupon the flask wasevacuated (0.10 mm Hg) and removed from the ice bath. Evacuation for onehour yielded a dry white solid powder of the water soluble surfactantSodium N_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysinate. [mp 47-55° C. tosmall droplets of clear colorless viscous liquid; IR (mineral oil mull,cm⁻¹), 3300m amide N—H str; 2188s, 2107s N═C str; 1627s, amide C═O str;1593s carboxylate C═O str]

Example III Preparation of a Two-Part Formulation for the Treatment ofPsoriasis

A two-part formulation for topical application to the skin was preparedas follows:

Part I: A 25% by mass mixture ofN_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysine in Dow Corning DC344 fluid(a mixture of octamethyl-cyclotetrasiloxane anddecamethyl-cyclopentasiloxane) was prepared in a mortar and pestle toproduce a paste that was loaded into a 5 ml plastic disposable syringe.A syringe needle was not employed. Rather, the dispensing end of thesyringe was capped except for when dispensing without a syringe needleinto the palm of a hand occurred.

Part II: Part II consisted of Cetaphil Moisturizing Lotion to whichadditional triethanol amine (TEA) was added such that the concentrationof the additional triethanol amine was 0.006 g triethanol amine per gramof lotion, raising the pH of the Cetaphil Lotion from 7.74 to 8.77.

Preferred Instructions for Application of Formulation to the Skin: A 0.2mL portion of the N_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysine/DC344mixture is dispensed from the syringe into the palm of a hand(approximately 0.13 g of the mixture). Next, two full squirts of theCetaphil/TEA lotion is dispensed on top of theN_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysine/DC344 mixture (approximately2.8 g of the lotion). Next, using the index finger of the other hand,the components are mixed thoroughly for approximately 30 seconds, duringwhich time the water insolubleN_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysine surfactant-precursor isdeprotonated to yield the water-soluble anionic (carboxylate) surfactantand yield a homogenous smooth white lotion (this reduces the pH to 7.4).This mixture is then applied to the afflicted areas by gently rubbing iton as one would apply any moisturizing lotion. Treatment is recommendedtwo to three times per day until the symptoms of the psoriasis subside.

Example IV Preparation of a One-Part Formulation for the Treatment ofPsoriasis

A one-part formulation for topical application to the skin was preparedas follows:

First, 0.00025% (by wt.; 5.0 micromolar) of SodiumN_(α)-lauroyl-N_(ε)-isothiocyanate-L-Lysinate, the sodium salt of thematerial provided in step three of Example II, was mixed with 2% LaurylPEG-10 Methyl Ether Dimethicone (commercially available from ClearChemical Corporation, Holland, Mich.) which was QS to achieve 100% with2,6,10,15,19,23-Hexamethyltetracosane (commercially available fromSigma-Aldrich). It will be understood that the concentration of SodiumN_(α)-lauroyl-N_(ε)-isothiocyanate-L-Lysinate may range fromapproximately 0.000001% to approximately 50%. Non-limiting examples ofadditional concentrations include 0.0005%, 0.005%, 0.005%, 0.005%,0.05%, 0.5%, 5%—just to name a few. It will be further understood thatthe concentration of Lauryl PEG-10 Methyl Ether Dimethicone may rangefrom approximately 0.000001% to approximately 50%.

Preferred Instructions for Application of the One-Part Formulation tothe Skin: A 0.1-1.0 mL portion of the one-part formulation is dispensedfrom a container into the palm of a hand for subsequent administrationto an affected area and/or is dispensed directly onto an affected areaby gently rubbing it on as one would apply a moisturizing lotion.Treatment is recommended one to four times per day until the symptoms ofthe psoriasis subside.

Example V Preparation of a One-Part Formulation for the Treatment ofPsoriasis

A one-part oil-based formulation for topical application to the skin wasprepared as follows:

Lyophilized Sodium N_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysinate (0.15g) is dissolved in 29.85 g of refined jojoba oil while stirring andwarming to 50° C. to give a clear colorless solution that is 0.50% bymass Sodium N_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysinate. Next, 0.10 gof this solution was combined with 69.90 g of refined jojoba oil, 20.0 gof heavy mineral oil, and 10.0 g of squalane to yield an oil-basedformulation that is 0.00050% by mass SodiumN_(α)-lauroyl-N_(ε)-isothiocyanato-L-Lysinate. The oils employed areprovided for the purposes of illustration, and are not to be construedas limiting the invention in any way. As such, the oils may be liquid,solid, or gel, and may be synthetic or of natural origin and include butare not limited to waxes, esters, lipids, fats, glycerides, cyclicsilicones, linear silicones, crosslinked silicones, alkylsilicones,silicone copolyols, alkylated silicone copolyols, and/or hydrocarbons,and/or ethoxylated versions of all of these.

The foregoing description merely explains and illustrates the inventionand the invention is not limited thereto except insofar as the appendedclaims are so limited, as those skilled in the art who have thedisclosure before them will be able to make modifications withoutdeparting from the scope of the invention.

What is claimed and desired to be secured by Letters Patent of theUnited States is:
 1. A method for treating psoriasis, comprising thestep(s) of: applying a surfactant or a pharmaceutically acceptable saltthereof to an area affected by psoriasis, wherein the protonated form ofthe surfactant consists of the following chemical structure: